Hepatic mRNA Expression Levels of the Oncogenes Alpha-Fetoprotein and Osteopontin as Diagnostics for Liver Cancer in a Murine Model of Diet-Induced Non-Alcoholic Steatohepatitis

• Published in: Processes Vol. 9; no. 9; p. 1516
• Main Authors: Pellicano, Anthony, Mullan, Stephanie, Goldberg, Itzhak, Narayan, Prakash
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2021
• Subjects: Animal models; Animals; Biomedical materials; Cytokeratin; Data points; Diagnostic systems; Diet; Epidemics; Fibrosis; Gene expression; Hepatocellular carcinoma; Hydroxyproline; Liver cancer; Oncogenes; Osteopontin; Sensitivity; Tumors; α-Fetoprotein; St Louis Missouri; United States > US
• ISSN: 2227-9717; 2227-9717
• DOI: 10.3390/pr9091516

Non-alcoholic steatohepatitis (NASH) is associated with an increased risk of hepatocellular carcinoma (HCC). Expression levels of hepatic oncogenes, alpha-fetoprotein (afp) and osteopontin (opn)/secreted phosphoprotein 1 (spp1), were investigated using a model of diet-induced NASH. Mice were randomized to a standard diet or a fast-food diet (FFD) for 17 months. Livers from the FFD cohort exhibited hallmark characteristics of NASH with liver fibrosis, with a subset of animals exhibiting HCC. Expression levels of hepatic afp and opn/spp1 were elevated ~2.5 and ~5-fold, respectively, in the FFD cohort. Hepatic opn/spp1 exhibited a direct (r = 0.65) and significant (p < 0.01) correlation with liver hydroxyproline content. Receiver operating characteristic (ROC) curve analysis for hepatic afp, as a diagnostic for HCC, returned an area under (AU) ROC 0.84, a sensitivity of 87.5%, a specificity of 77% and a threshold of >1.05-fold change in mRNA level. The use of hepatic opn/ssp1 as a diagnostic for HCC returned an AUROC 0.88, a sensitivity of 83.3%, a specificity of 86.7% and a threshold of >2.4-fold change in mRNA level. These data point to a transformation of NASH to an oncotype with hepatic oncogene levels as a diagnostic for NASH.